Grant Number:	1R01CA302879-01A1 Interpret this number
Primary Investigator:	Modugno, Francesmary
Organization:	University Of Pittsburgh At Pittsburgh
Project Title:	Immune Dysfunction, Social Determinants of Health, and Ovarian Cancer Outcome Differences
Fiscal Year:	2026

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with a 5-year survival of about 50%. Aggressive surgery plus platinum-based chemotherapy remains the standard of care treatment. Despite well- established treatment guidelines, there are significant racial disparities in EOC survival: Black women have significantly higher mortality (40% 5-year survival) and have not had the survival improvement over the last few decades experienced by White women. Failure to receive guideline-concordant care (GCC), reduced access to care, and treatment delays further widen the survival gap. However, even among women with equal access receiving GCC and controlling for known factors contributing to disparities such as social determinants of health, age, cancer stage, and tumor histology, survival for Black women remains significantly worse. Understanding the underlying biological mechanisms of these disparities and how host and societal factors interact to impact these mechanisms is an urgent, unmet need. Based on preclinical data and compelling preliminary data from our group, we hypothesize that dysregulated anti-tumor immunity underlies racial disparities in outcomes and that this dysregulation is caused by a woman’s response to systemic and social factors that are more frequently experienced by Black women. Accordingly, we will pursue three specific aims utilizing our unique cohort of women with newly diagnosed EOC. In Aim 1, we will examine the difference in anti-tumor immunity within the tumor-immune microenvironment (TIME). We will evaluate phenotypes according to well-established treatment response and survival metrics overall and by both self-identified race and genetic ancestry to identify TIME signatures predictive of patient outcomes in general, as well as racial differences in outcomes. In Aim 2, we will examine systemic anti-tumor immunity. We will compare systemic anti-tumor profiles according to well-established treatment response and survival metrics overall and by both self-identified race and genetic ancestry to identify antitumor markers predictive of outcomes in general, as well as racial differences in outcomes. Aim 3 will utilize patient-derived organoid models to assess potential mechanistic drivers of dysregulated anti-tumor immunity. We will also characterize women using markers of lifetime stress and residential context. We will then explore the association of these markers with antitumor immunity overall and by both race and genetic ancestry to identify biological and non-biological factors contributing to observed racial disparities in EOC outcomes. Establishing the role of antitumor immunity in EOC outcomes and defining how individual and societal factors impact those relationships are crucial first steps in addressing EOC disparities. Findings from our research will identify novel targets that can be used in the future to develop interventions that will open new doors for improving EOC outcomes, especially for Black women.





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